Effect of uraemic toxins of vascular reactivity

Research Opportunity
Honours, Master of Biomedical Science
Project Status
Future
Department
Medicine and Radiology
Location
St Vincent's Hospital
Supervisor Email Number Webpage
Dr Andrew Kompa akompa@unimelb.edu.au Personal web page
Dr Michael Zhang Personal web page

Project Details

Cardiovascular disease in the setting of chronic kidney disease (CKD) displays unique characteristics, primarily left ventricular (LV) hypertrophy with extensive interstitial fibrosis as well as endothelial dysfunction, arterial stiffness, calcification and inflammation, collectively termed ‘uraemic cardiomyopathy’. Uraemic toxins are elevated in the circulation of patients with CKD, and due to their strong binding affinity to serum proteins (ie albumin), they are unable to be removed from the circulation even by conventional dialysis, being too large to pass through the pore o the dialysis membrane.

Indoxyl sulphate (IS) is one such uraemic toxin that has been extensively examined in cells and animal models of disease. IS has been demonstrated to exert deleterious effects in cardiac, renal, vascular and immune cells, and in tissues from man and animal models.

Recently an intracellular receptor for IS was identified, the aryl hydrocarbon receptor (AhR), a cytosolic ligand-dependent transcription factor mediating numerous biological processes including inflammation, vascular remodeling, and atherosclerosis. IS activation of this receptor is known to target the oxidative stress pathway by both genomic and non-genomic mechanisms.

This project will assess the vascular reactivity of aortic vessels exposed to the uraemic toxin IS and its inhibition using selective AhR antagonists methoxy-nitro-flavone (MNF) and CH223191 in aortic rings. Following experiments the endothelium will be examined using immunohistochemistry. This project will potentially identify a novel agent to treat vascular and inflammatory changes in patients’ with CKD.


School Research Themes

Cardiometabolic



Research Opportunities

Honours, Master of Biomedical Science Graduate Research Students who are interested in joining this project will need to consider their elegibility as well as other Graduate Research requirements before contacting the supervisor of this research

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Key Contact

For further information about this research, please contact a supervisor.

Department

Medicine and Radiology

Research Group / Unit / Centre

Biomedical Translational Research Group: Developing Therapies for Cardiovascular Disease

Research Node

St Vincent's Hospital